Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2188-91. doi: 10.1016/j.bmcl.2011.03.018.

Abstract

To explore more potent N-acylimidazole analogues of CDDO than CDDO-Im, which is one of the most potent compounds in several widely used bioassays related to protection against inflammation and carcinogenesis; we have synthesized and evaluated five new N-acyl(acetylenic)imidazole analogues. Among them, 4-ethynylimidazole 4 is nearly equivalent to CDDO-Im in potency in these bioassays. Remarkably, the solid form of 4 is more stable than that of CDDO-Im. These findings suggest that 4 is a very promising anti-inflammatory and cytoprotective agent and its further preclinical evaluation is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line, Tumor
  • Cytoprotection / drug effects
  • Heme Oxygenase-1 / metabolism
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology
  • Interferon-gamma / metabolism
  • Mice
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Nitric Oxide / metabolism
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemical synthesis
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology

Substances

  • 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl)-4-ethynylimidazole
  • 1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole
  • Anti-Inflammatory Agents
  • Imidazoles
  • Nitric Oxide
  • Oleanolic Acid
  • Interferon-gamma
  • Heme Oxygenase-1
  • NAD(P)H Dehydrogenase (Quinone)
  • Nqo1 protein, mouse